FAS/FAS-L dependent killing of activated human monocytes and macrophages by CD4+CD25- responder T cells, but not CD4+CD25+ regulatory T cells

Jagger, A. L. et al. (2012) FAS/FAS-L dependent killing of activated human monocytes and macrophages by CD4+CD25- responder T cells, but not CD4+CD25+ regulatory T cells. Journal of Autoimmunity, 38(1), pp. 29-38. (doi:10.1016/j.jaut.2011.11.015) (PMID:22197557)

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Abstract

Conclusive resolution of an immune response is critical for the prevention of autoimmunity and chronic inflammation. We report that following co-culture with autologous CD4+CD25- responder T cells, human CD14+ monocytes and monocyte-derived macrophages become activated but also significantly more prone to apoptosis than monocytes/macrophages cultured alone. In contrast, in the presence of CD4+CD25+ regulatory T cells (Tregs), monocytes and macrophages survive whilst adopting an anti-inflammatory phenotype. The induction of monocyte death requires responder T cell activation and cell-contact between responder T cells and monocytes. We demonstrate a critical role for FAS/FAS-L ligation in responder T cell-induced monocyte killing since responder T cells, but not Tregs, upregulate FAS-ligand (FAS-L) mRNA, and induce FAS expression on monocytes. Furthermore, responder T cell-induced monocyte apoptosis is blocked by neutralising FAS/FAS-L interaction, and is not observed when monocytes from an autoimmune lymphoproliferative syndrome (ALPS) patient with complete FAS-deficiency are used as target cells. Finally, we show that responder T cell-induced killing of monocytes is impaired in patients with active rheumatoid arthritis (RA). Our data suggest that resolution of inflammation in the course of a healthy immune response is aided by the unperturbed killing of monocytes with inflammatory potential by responder T cells and the induction of longer-lived, Treg-induced, anti-inflammatory monocytes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gracie, Professor J Alastair
Authors: Jagger, A. L., Evans, H. G., Walter, G. J., Gullick, N. J., Menon, B., Ballantine, L. E., Gracie, A., Magerus-Chatinet, A., Tiemessen, M., Geissmann, F., Rieux-Laucat, F., and Taams, L. S.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Research Group:Taams
Journal Name:Journal of Autoimmunity
Journal Abbr.:J. Autoimmun
Publisher:Elsevier
ISSN:0896-8411
ISSN (Online):1095-9157
Published Online:24 December 2011

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